title: Gene duplication and neofunctionalization: POLR3G and POLR3GL.
abstract: RNA polymerase III (Pol III) occurs in two versions, one containing the POLR3G subunit and the other the closely related POLR3GL subunit. It is not clear whether these two Pol III forms have the same function, in particular whether they recognize the same target genes. We show that the POLR3G and POLR3GL genes arose from a DNA-based gene duplication, probably in a common ancestor of vertebrates. POLR3G- as well as POLR3GL-containing Pol III are present in cultured cell lines and in normal mouse liver, although the relative amounts of the two forms vary, with the POLR3G-containing Pol III relatively more abundant in dividing cells. Genome-wide chromatin immunoprecipitations followed by high-throughput sequencing (ChIP-seq) reveal that both forms of Pol III occupy the same target genes, in very constant proportions within one cell line, suggesting that the two forms of Pol III have a similar function with regard to specificity for target genes. In contrast, the POLR3G promoter--not the POLR3GL promoter--binds the transcription factor MYC, as do all other promoters of genes encoding Pol III subunits. Thus, the POLR3G/POLR3GL duplication did not lead to neo-functionalization of the gene product (at least with regard to target gene specificity) but rather to neo-functionalization of the transcription units, which acquired different mechanisms of regulation, thus likely affording greater regulation potential to the cell.
authors.affiliation: Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland;
authors.forename: Marianne
authors.initials: M
authors.lastname: Renaud
authors.forename: Viviane
authors.initials: V
authors.lastname: Praz
authors.forename: Erwann
authors.initials: E
authors.lastname: Vieu
authors.forename: Laurence
authors.initials: L
authors.lastname: Florens
authors.forename: Michael P
authors.initials: MP
authors.lastname: Washburn
authors.forename: Philippe
authors.initials: P
authors.lastname: l'Hôte
authors.forename: Nouria
authors.initials: N
authors.lastname: Hernandez
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D019143:Evolution, Molecular; D020440:Gene Duplication; D016678:Genome; D006367:HeLa Cells; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010802:Phylogeny; D011401:Promoter Regions, Genetic; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012320:RNA Polymerase III / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D016415:Sequence Alignment; D014714:Vertebrates / Q000235:genetics
chemical_list: D002843:Chromatin; C489428:Myc protein, mouse; D021122:Protein Subunits; D016271:Proto-Oncogene Proteins c-myc; C569418:POLR3G protein, human; C569417:POLR3G protein, mouse; D012320:RNA Polymerase III